Dual antiplatelet therapy (DAPT) with acetylsalicylic acid and an inhibitor of the adenosine diphosphate platelet receptor P2Y12 has been shown to reduce the risk of stent thrombosis (ST), myocardial infarction and cardiac death after percutaneous coronary intervention (PCI) with bare-metal stents (BMS) and drug-eluting stents (DES). However, while there is consensus on 1-month DAPT after BMS, the optimal duration and the risk-benefit ratio of DAPT duration after DES implantation remains controversial. Controversy surrounding this issue is demonstrated by differences in guideline recommendations for DAPT duration after PCI with DES. For example, while the ACC/AHA recommends a minimum of 12 months, ESC guidelines recommend at least 6 months of DAPT. Recent reports suggest that 6 months of DAPT after second-generation DES implantation might be safe compared with longer durations. Large randomized controlled trials powered to examine ST and bleeding events are currently ongoing and will shed novel insight on unresolved concerns and inform medical practice in the foreseeable future. In the present review, we critically and comprehensively examine the current level of evidence regarding the optimal duration of DAPT after PCI with DES and illustrate new and future perspectives surrounding this rapidly changing field.